CA2404235A1 - Cell-specific adenovirus vectors comprising an internal ribosome entry site - Google Patents
Cell-specific adenovirus vectors comprising an internal ribosome entry site Download PDFInfo
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- CA2404235A1 CA2404235A1 CA002404235A CA2404235A CA2404235A1 CA 2404235 A1 CA2404235 A1 CA 2404235A1 CA 002404235 A CA002404235 A CA 002404235A CA 2404235 A CA2404235 A CA 2404235A CA 2404235 A1 CA2404235 A1 CA 2404235A1
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/63—Introduction of foreign genetic material using vectors; Vectors; Use of hosts therefor; Regulation of expression
- C12N15/79—Vectors or expression systems specially adapted for eukaryotic hosts
- C12N15/85—Vectors or expression systems specially adapted for eukaryotic hosts for animal cells
- C12N15/86—Viral vectors
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K48/00—Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
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- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
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- C12N2710/00—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA dsDNA viruses
- C12N2710/00011—Details
- C12N2710/10011—Adenoviridae
- C12N2710/10311—Mastadenovirus, e.g. human or simian adenoviruses
- C12N2710/10341—Use of virus, viral particle or viral elements as a vector
- C12N2710/10343—Use of virus, viral particle or viral elements as a vector viral genome or elements thereof as genetic vector
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/001—Vector systems having a special element relevant for transcription controllable enhancer/promoter combination
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/008—Vector systems having a special element relevant for transcription cell type or tissue specific enhancer/promoter combination
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2830/00—Vector systems having a special element relevant for transcription
- C12N2830/80—Vector systems having a special element relevant for transcription from vertebrates
- C12N2830/85—Vector systems having a special element relevant for transcription from vertebrates mammalian
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- C—CHEMISTRY; METALLURGY
- C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
- C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
- C12N2840/00—Vectors comprising a special translation-regulating system
- C12N2840/20—Vectors comprising a special translation-regulating system translation of more than one cistron
- C12N2840/203—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES
- C12N2840/206—Vectors comprising a special translation-regulating system translation of more than one cistron having an IRES having multiple IRES
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- Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
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- Bioinformatics & Cheminformatics (AREA)
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- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
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- Medicines Containing Material From Animals Or Micro-Organisms (AREA)
- Micro-Organisms Or Cultivation Processes Thereof (AREA)
- Investigating Or Analysing Biological Materials (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Disclosed herein are replication-competent adenovirus vectors comprising co-transcribed first and second genes under transcriptional control of a heterologous, target cell-specific transcriptional regulatory element (TRE), wherein the second gene is under translational control of an internal ribosome entry site. Methods for the preparation and use of such vectors are also provided. The vectors provide target cell-specific virus replication in applications such as cancer therapy and gene therapy.
Claims (58)
1. A replication-competent adenovirus vector comprising first and second genes co-transcribed as a single mRNA wherein the first and the second genes are under transcriptional control of a heterologous, target cell-specific transcriptional regulatory element (TRE), wherein the second gene has a mutation in or deletion of its endogenous promoter and is under translational control of an internal ribosome entry site (IRES) and wherein said vector exhibits greater specificity for the target cell than an adenovirus vector comprising a target cell-specific THE operably linked to a gene and lacking an IRES.
2. The vector of Claim 1, wherein at least one of said first and second genes is an adenovirus gene.
3. The vector of Claim 2, wherein both of said first and said second genes are adenovirus genes.
4. The vector of Claim 2, wherein at least one of said first and said second adenovirus gene is essential for viral replication.
5. The vector of Claim 4, wherein the adenovirus gene essential for viral-replication is an adenovirus early gene.
6. The vector of Claim 5, wherein the adenovirus early gene includes ElA, E1B, E2, or E4.
7. The vector of Claim 4, wherein the adenovirus gene essential for viral replication is an adenovirus late gene.
8. The vector of Claim 3, wherein both said first and said second adenovirus genes are essential for viral replication.
9. The vector of Claim 8, wherein at least one of said first and said second adenovirus genes is an adenovirus early gene.
10. The vector of Claim 8, wherein at least one of said first and said second adenovirus genes is an adenovirus late gene.
11. The vector of Claim 8, wherein said first adenovirus gene is ElA and said second adenovirus gene is E1B.
12. The vector of Claim 11 wherein E1A has its endogenous promoter deleted.
13. The vector of Claim 11 wherein E1A has an inactivation of ElA enhancer I
14. The vector of Claim 11 wherein E1B has an inactivation of its endogenous promoter.
15. The vector of Claim 11 wherein E1B has a deletion of the 19-kDa region.
16. The vector of Claim 11 wherein E1A has an inactivation of its endogenous promoter and ElB has an inactivation of its endogenous promoter.
17. The vector of Claim 16 wherein E1B has a deletion of the 19-kDa region.
18. The vector of Claim 16 wherein E1A has an inactivation of E1A enhancer I.
19. The vector of Claim 1, wherein the internal ribosome entry site (IRES) is from EMCV.
20. The vector of Claim 1 wherein the IRES is from VEGF.
21. The vector of Claim 1 wherein the IRES includes the 5'UTR of HCV; the 5' UTR of BiP; or the 5'UTR of PDGF.
22. The vector of Claim 1, wherein the TRE is specific for a target cell that is a cancer cell.
23. The vector of Claim 22 wherein the cancer cell includes a prostate cancer cell, a breast cancer cell, a hepatoma cell, a melanoma cell, a bladder cell or a colon cancer cell.
24. The vector of Claim 22, wherein the TRE includes the probasin (PB) TRE, the prostate-specific antigen (PSA) TRE, the mucin (MUC1) TRE, the .alpha.-fetoprotein (AFP) TRE, the hKLK2 TRE, the tyrosinase TRE, the human uroplakin II (hUPII) THE or the carcinoembryonic antigen (CEA) TRE.
25. The vector of Claim 9 wherein said first adenovirus gene has a deletion of its endogenous promoter.
26. The vector of Claim 25 wherein said first adenovirus gene is E1A.
27. The vector of Claim 9 wherein said first and/or said second adenovirus gene has a deletion of an enhancer region.
28. The vector of Claim 27 wherein said first gene is E1A and said enhancer is E1A enhancer I.
29. The vector of Claim 1 wherein said TRE has an endogenous silencer element deleted.
30. The vector of Claim 1 wherein said adenovirus vector comprises an E3 region.
31. The adenovirus vector of Claim 11 wherein said adenovirus comprises an E3 region.
32. The adenovirus vector of Claim 11 further comprising a transgene.
33. An adenovirus vector comprising a gene under transcriptional control of a melanocyte-specific TRE.
34. The vector of Claim 33 wherein said gene is an adenoviral gene.
35. The vector of Claim 34 wherein said adenoviral gene is a gene essential for replication.
36. The vector of Claim 32 wherein said transgene is co-transcribed with said first and said second gene and said transgene is under the translation control of a separate internal ribosome entry site (IRES).
37. The vector of Claim 36 wherein said IRES is from EMCV.
38. The vector of Claim 36 wherein said IRES is from VEGF.
39. The vector of Claim 30 further comprising an adenovirus death protein gene (ADP).
40. The vector of Claim 32 wherein said transgene is a cytotoxic gene.
41. The vector of Claim 1 wherein said first adenovirus gene is essential for viral replication and said second adenovirus gene is the adenovirus death protein gene (ADP).
42. The vector of Claim 41 wherein said first adenovirus gene is E1A.
43. The vector of Claim 42 wherein E1A has a deletion of its endogenous promoter.
44. The vector of Claim 42 wherein said E1A has a deletion of E1A enhancer I.
45. The vector of Claim 1 wherein said first gene is essential for viral replication and said second gene is E3.
46. The vector of Claim 45 wherein said first gene is E1A.
47. A composition comprising a vector according to Claim 1.
48. The composition of Claim 47 further comprising a pharmaceutically acceptable excipient.
49. A composition comprising a vector according to Claim 30.
50. The composition of Claim 49 further comprising a pharmaceutically acceptable excipient.
51. A host cell comprising the vector of Claim 1.
52. A host cell comprising the vector of Claim 30.
53. An adenovirus vector comprising E1B under transcriptional control of a heterologous, target cell specific TRE, wherein E1B has a deletion of part or all of the 19-kDa region.
54. A host cell comprising the adenovirus vector of claim 53.
55. A method for propagating a replication-competent adenovirus vector comprising a target cell-specific TRE, said method comprising combining an adenovirus vector of Claim 1 with mammalian cells that permit the function of a target cell-specific TRE, such that the adenovirus vector enters the cell, whereby said adenovirus vector is propagated.
56. A method for conferring selective cytotoxicity in target cells, comprising contacting the cells with an adenovirus vector of Claim 41 whereby the vector enters the cell.
57. A method for modifying the genotype of a target cell, comprising contacting the cell with an adenovirus vector of Claim 1, wherein the vector enters the cell.
58. A method for suppressing tumor cell growth, comprising contacting a tumor cell with an adenovirus vector of Claim 41 such that the adenovirus vector enters the tumor cell and exhibits selective cytotoxicity for the tumor cell.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US19215600P | 2000-03-24 | 2000-03-24 | |
US60/192,156 | 2000-03-24 | ||
PCT/US2001/009036 WO2001073093A2 (en) | 2000-03-24 | 2001-03-21 | Cell-specific adenovirus vectors comprising an internal ribosome entry site |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2404235A1 true CA2404235A1 (en) | 2001-10-04 |
CA2404235C CA2404235C (en) | 2010-09-21 |
Family
ID=22708488
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA2404235A Expired - Lifetime CA2404235C (en) | 2000-03-24 | 2001-03-21 | Cell-specific adenovirus vectors comprising an internal ribosome entry site |
Country Status (7)
Country | Link |
---|---|
EP (1) | EP1266022B1 (en) |
JP (1) | JP2004511203A (en) |
AT (1) | ATE412058T1 (en) |
AU (2) | AU4764801A (en) |
CA (1) | CA2404235C (en) |
DE (1) | DE60136268D1 (en) |
WO (1) | WO2001073093A2 (en) |
Families Citing this family (14)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6673614B2 (en) | 2000-06-27 | 2004-01-06 | Cell Genesys, Inc. | Rapid methods and kits for detection and semi-quantitation of anti-adenovirus antibody |
EP1377672A2 (en) | 2001-02-23 | 2004-01-07 | Novartis AG | Vector constructs |
US8163892B2 (en) | 2002-07-08 | 2012-04-24 | Oncolys Biopharma, Inc. | Oncolytic virus replicating selectively in tumor cells |
JP3867968B2 (en) * | 2002-07-08 | 2007-01-17 | 関西ティー・エル・オー株式会社 | Oncolytic virus that selectively grows in tumor cells |
WO2004042025A2 (en) | 2002-11-01 | 2004-05-21 | Cell Genesys, Inc. | Cell-specific adenovirus vector comprising ebv-specific promoter |
JP4478775B2 (en) * | 2003-07-31 | 2010-06-09 | 財団法人名古屋産業科学研究所 | Efficient production method of growth control type recombinant adenovirus vector and kit for production thereof |
US7482156B2 (en) | 2003-10-15 | 2009-01-27 | Cell Genesys, Inc. | Hepatocellular carcinoma specific promoter and uses thereof |
EP1900749A1 (en) * | 2006-09-12 | 2008-03-19 | Institut National De La Sante Et De La Recherche Medicale (Inserm) | Nucleic acids for expressing a polynucleotide of interest in mammalian cancer cells |
EP2971008B1 (en) | 2013-03-14 | 2018-07-25 | Salk Institute for Biological Studies | Oncolytic adenovirus compositions |
KR102471633B1 (en) | 2016-02-23 | 2022-11-25 | 솔크 인스티튜트 포 바이올로지칼 스터디즈 | Exogenous gene expression in therapeutic adenovirus for minimal impact on viral kinetics |
EP3390428B1 (en) | 2016-02-23 | 2019-09-25 | Salk Institute for Biological Studies | High throughput assay for measuring adenovirus replication kinetics |
JP7208492B2 (en) | 2016-03-10 | 2023-01-19 | シージー オンコロジー, インコーポレイテッド | Methods of treating solid tumors or lymphoid tumors with combination therapy |
AU2017375633C1 (en) | 2016-12-12 | 2023-04-27 | Salk Institute For Biological Studies | Tumor-targeting synthetic adenoviruses and uses thereof |
WO2018191654A1 (en) | 2017-04-14 | 2018-10-18 | Cold Genesys, Inc. | Methods of treating bladder cancer |
Family Cites Families (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6638762B1 (en) * | 1994-11-28 | 2003-10-28 | Genetic Therapy, Inc. | Tissue-vectors specific replication and gene expression |
US6197293B1 (en) * | 1997-03-03 | 2001-03-06 | Calydon, Inc. | Adenovirus vectors specific for cells expressing androgen receptor and methods of use thereof |
FR2755975B1 (en) * | 1996-11-15 | 1999-05-07 | Rhone Poulenc Rorer Sa | BICISTRONIC RECOMBINANT VIRUSES USEFUL FOR THE TREATMENT OF DYSLIPOPROTEINEMIA-RELATED CONDITIONS |
WO1998037189A1 (en) * | 1997-02-25 | 1998-08-27 | Qbi Enterprises Ltd. | Ires sequences with high translational efficiency and expression vectors containing the sequence |
AU744725B2 (en) * | 1997-03-03 | 2002-02-28 | Cold Genesys, Inc. | Adenovirus vectors containing heterologous transcription regulatory elements and methods of using same |
WO1998039467A2 (en) * | 1997-03-03 | 1998-09-11 | Calydon, Inc. | Adenovirus vectors specific for cells expressing carcinoembryonic antigen and methods of use thereof |
FR2762615B1 (en) * | 1997-04-28 | 1999-07-16 | Inst Nat Sante Rech Med | NEW INTERNAL RIBOSOME ENTRY SITE AND VECTOR CONTAINING THE SAME |
ATE376062T1 (en) * | 1997-08-04 | 2007-11-15 | Cell Genesys Inc | ENHANCER OF HUMAN GLANDULAR KALLIC CLEANING, VECTORS CONTAINING IT AND METHODS OF ITS USE |
EP1070122A4 (en) * | 1998-03-11 | 2004-11-10 | Univ Texas | Induction of apoptic or cytotoxic gene expression by adenoviral mediated gene codelivery |
JP2002506651A (en) * | 1998-03-16 | 2002-03-05 | イントロジェン・セラピューティクス,インコーポレイテッド | Multi-gene vector |
US6900049B2 (en) * | 1998-09-10 | 2005-05-31 | Cell Genesys, Inc. | Adenovirus vectors containing cell status-specific response elements and methods of use thereof |
CA2404060A1 (en) * | 2000-03-24 | 2001-10-04 | Cell Genesys, Inc. | Methods of treating neoplasia with combinations of target cell-specific adenovirus, chemotherapy and radiation |
-
2001
- 2001-03-21 AU AU4764801A patent/AU4764801A/en active Pending
- 2001-03-21 CA CA2404235A patent/CA2404235C/en not_active Expired - Lifetime
- 2001-03-21 AU AU2001247648A patent/AU2001247648B2/en not_active Expired
- 2001-03-21 WO PCT/US2001/009036 patent/WO2001073093A2/en active Application Filing
- 2001-03-21 JP JP2001570809A patent/JP2004511203A/en active Pending
- 2001-03-21 AT AT01920614T patent/ATE412058T1/en not_active IP Right Cessation
- 2001-03-21 DE DE60136268T patent/DE60136268D1/en not_active Expired - Lifetime
- 2001-03-21 EP EP01920614A patent/EP1266022B1/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
WO2001073093A2 (en) | 2001-10-04 |
AU4764801A (en) | 2001-10-08 |
CA2404235C (en) | 2010-09-21 |
JP2004511203A (en) | 2004-04-15 |
DE60136268D1 (en) | 2008-12-04 |
EP1266022A2 (en) | 2002-12-18 |
WO2001073093A3 (en) | 2002-09-06 |
AU2001247648B2 (en) | 2006-03-30 |
ATE412058T1 (en) | 2008-11-15 |
EP1266022B1 (en) | 2008-10-22 |
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